E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
subjects with moderate or severe atopic dermatitis. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the efficacy of GW870086X cream (0.2% and 2%) applied once daily for 21 days on diseased skin of adult subjects with atopic dermatitis using the Three Item Severity (TIS) scale on Day 22. |
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E.2.2 | Secondary objectives of the trial |
• To investigate the efficacy of GW870086X cream (0.2% and 2%) applied once daily for 21 days on diseased skin of adult subjects with atopic dermatitis using the Three Item Severity (TIS) scale on Days 2, 3, 7 and 14. • To investigate the efficacy of GW870086X cream (0.2% and 2%) applied once daily for 21 days on diseased skin of adult subjects with atopic dermatitis using the Investigators Global Assessment scale (IGA) for atopic dermatitis. • To investigate the safety and tolerability of GW870086X cream (0.2% and 2%) applied once daily for 21 days on diseased skin of adult subjects with atopic dermatitis. • To assess the pharmacokinetic parameters of GW870086X cream (0.2% and 2%) applied once daily for 21 days. • To assess skin biopsy pharmacodynamic markers of GW870086X cream (0.2% and 2%) applied once daily for 21 days.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects with a diagnosis of atopic dermatitis who are otherwise healthy. Diagnosis of atopic dermatitis: • Subject must have a documented history of atopic dermatitis as defined by Hanifin and Rajka and modified by Williams et al [Williams, 1994]. • Subject must present with moderate to severe atopic dermatitis as defined by a score of >25 using the modified SCORAD rating scale. • Subject must have at least 3 index lesions (=> 1cm2 in size) with a sum score of =>4 and <=6 for erythema, oedema/papulation and excoriations using the TIS rating scale. The index lesions will be selected from the subject’s extremities and should represent common lesions i.e. not the most or least severe lesions. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. 2. Male or female between 18 and 65 years of age inclusive, at the time of signing the informed consent. 3. A female subject is eligible to participate if she is of: • Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. 4. Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication until 90-95 hours post dose. 5. BMI within the range 19.0 – 29.0 kg/m2 (inclusive). 6. Subjects must have body surface area (BSA) disease involvement of >5% as assessed by the rule of nines method. 7. Patients must be willing to refrain from current active therapy for at least 10 days prior to dosing, 8. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. 9. Single QTc, QTcB < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block. 10. AST and ALT < 2xULN; alkaline phosphatase and bilirubin <=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
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E.4 | Principal exclusion criteria |
1. The subject presents with any systemic disorder or active skin disease (other than atopic dermatitis) (e.g. psoriasis) that would in any way confound interpretation of the study results or subjects who present with scars, moles, tattoos, body piercings, sunburn in the test area which could interfere with the assessment of lesions at screening. 2. The subject has atopic dermatitis restricted to the face, the feet or the hands only. 3. The subject has a current complication of atopic dermatitis such as erythroderma or overt bacterial or viral infection for which treatment with anti-infectives are indicated. 4. History of recent (< 6 months) active or presence of current superficial skin infections of viral aetiology such as herpes simplex, or varicella. 5. The subject has been diagnosed as having contact dermatitis in area of target lesions, seborrheic dermatitis and/or occupational eczema at predilection sites of atopic dermatitis. 6. The subject has had topical or transdermal treatments, such as but not limited to retinoids, nicotine or hormone replacement therapies, on or near the intended site of application within 14 days prior to first application of study medication. Use of other topical preparations such as those containing vitamins, supplements or herbal within 14 days prior to application. 7. The subject has had systemic treatment for atopic dermatitis (including corticosteroids, cyclosporine, tacrolimus, methotrexate, PUVA, or UVB) within 28 days of the first dose of study medication. 8. Foreseeable intensive UV exposure during the study (solar or artificial). Subjects must not be exposed to direct sunlight or skin tanning devices (e.g. sunbed) for the duration of the study. 9. The subject has used topical treatment with tar or any corticosteroid within 14 days of the first dose of study medication except topical 1% hydrocortisone which may be used twice daily in patients with severe disease who require step-down therapy during the wash-out period until 3 days prior to study start, after which the hydrocortisone must be discontinued. 10. The subject has used topical treatment with buproprion within 14 days of the first dose of study medication. 11. History of cutaneous photodisorder, such as photoallergic reaction or polymorphic light eruption. 12. History of allergy to steroids or components of test medications, including vaseline, emollient or specific soap and adhesives to be used in the study that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation. 13. History or presence of skin (other than atopic dermatitis), hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs. 14. Subjects with a history of diaphoresis/excessive sweating not restricted to palms or face. 15. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening 16. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). 17. A positive pre-study drug/alcohol screen. 18. A positive test for HIV antibody. 19. History of regular alcohol consumption within 6 months of the study defined as: • An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits. 20. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). 21. Exposure to more than four new chemical entities within 12 months prior to the first dosing day. 22. Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. 23. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. 24. Unwillingness or inability to follow the procedures outlined in the protocol. 25. Subject is mentally or legally incapacitated. 26. History of sensitivity to heparin or heparin-induced thrombocytopenia. 27. Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline TIS scores between GW870086X (0.2% and 2%) versus placebo at Day 22. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |